title: Identification of a high affinity FcgammaRIIA-binding peptide that distinguishes FcgammaRIIA from FcgammaRIIB and exploits FcgammaRIIA-mediated phagocytosis and degradation.
abstract: FcgammaRIIA is a key activating receptor linking immune complex formation with cellular effector functions. FcgammaRIIA has 93% identity with an inhibitory receptor, FcgammaRIIB, which negatively regulates FcgammaRIIA. FcgammaRIIA is important in the therapeutic action of several monoclonal antibodies. Binding molecules that discriminate FcgammaRIIA from FcgammaRIIB may optimize receptor activity and serve as a lead for development of therapeutics with FcgammaRIIA as a key target. Here we report the use of phage display libraries to select short peptides with distinct FcgammaRIIA binding properties. An 11-mer peptide (WAWVWLTETAV) was characterized that bound FcgammaRIIA with a K(d) of 500 nm. It mediated cell internalization and degradation of a model antigen. The peptide-binding site on FcgammaRIIA was shown to involve Phe(163) and the IgG binding amino acids Trp(90) and Trp(113). It is thus overlapping but not identical to that of IgG. Neither activating receptors FcgammaRI and FcgammaRIII, nor FcgammaRIIB, all of which lack Phe(163), bound the peptide.
authors.affiliation: Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Gøril
authors.initials: G
authors.lastname: Berntzen
authors.forename: Jan Terje
authors.initials: JT
authors.lastname: Andersen
authors.forename: Kristine
authors.initials: K
authors.lastname: Ustgård
authors.forename: Terje E
authors.initials: TE
authors.lastname: Michaelsen
authors.forename: Seyed Ali
authors.initials: SA
authors.lastname: Mousavi
authors.forename: Julie Dee
authors.initials: JD
authors.lastname: Qian
authors.forename: Per Eugen
authors.initials: PE
authors.lastname: Kristiansen
authors.forename: Vigdis
authors.initials: V
authors.lastname: Lauvrak
authors.forename: Inger
authors.initials: I
authors.lastname: Sandlie
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010587:Phagocytosis; D017434:Protein Structure, Tertiary; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: C080568:Fc gamma receptor IIA; C080571:Fc gamma receptor IIB; D010455:Peptides; D017452:Receptors, IgG; D011994:Recombinant Proteins